Systems and methods for applying a selected treatment agent into contact with tissue

ABSTRACT

Systems and methods that treat disorders of the gastrointestinal tract by applying one or more treatment agents to tissue at or near the region where abnormal neurological symptoms or abnormal tissue conditions exist. The treatment agent is selected to either disrupt the abnormal nerve pathways and/or to alleviate the abnormal tissue conditions. The treatment agent can include at least one cytokine and/or at least one vanilloid compound to evoke a desired tissue response. The systems and methods can be used a primary treatment modality, or as a neoadjuvent or adjuvant treatment modality.

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.10/912,268, filed Aug. 5, 2004 (now U.S. Pat. No. 7,293,563), which isdivisional of U.S. patent application Ser. No. 09/994,375, filed Nov.26, 2001 (now U.S. Pat. No. 6,790,207, which is a continuation-in-partof U.S. patent application Ser. No. 09/304,737, filed May 4, 1999, nowU.S. Pat. No. 6,464,697, and a continuation-in-part of U.S. patentapplication Ser. No. 09/090,794, filed Jun. 4, 1998 and entitled “Methodfor Treating a Sphincter” (now abandoned).

FIELD OF THE INVENTION

In a general sense, the invention is directed to systems and methods fortreating interior tissue regions of the body. More specifically, theinvention is directed to systems and methods for treating dysfunctionsof organs and tissue in the gastrointestinal tract.

BACKGROUND OF THE INVENTION

Disorders of organs or tissue of the gastrointestinal tract can becaused by as neurological factors (such as abnormal nerve impulses) orby physical factors (such as excess tissue volume).

For example, intestinal motility (i.e., the contraction of intestinalmuscles and the propulsion and movement of the lumenal contents) iscontrolled by nerves and hormones, as well as by electrical activity inthe muscular wall of the intestine. There are several disorders thatinvolve abnormal motility and result in abnormal and uncomfortablevisceral sensations. These disorders can cause significant discomfortand distress in the absence of gross physical abnormality of theintestine.

For example, irritable bowel syndrome (IBS) is a common disorder of theintestines. IBS can lead to crampy pain, gassiness, bloating, andchanges in bowel habits. Some people with IBS have constipation(difficult or infrequent bowel movements) others have diarrhea (frequentloose stools, often with an urgent need to move the bowels); and somepeople experience both symptoms intermittently. Sometimes the personwith IBS has a crampy urge to move the bowels, but cannot do so. Thecause of IBS is not known, and as yet there is no cure. IBS can becharacterized as a functional disorder because there is no sign ofdisease when the intestine is examined, often IBS is just a mildannoyance, but for some people it can be disabling.

Dyspepsia is another example. Dyspepsia is literally translated as ‘baddigestion” and is commonly known as indigestion. Motility-like dyspepsiacauses persistent or recurring abdominal pain that is centered in theupper abdomen. People with motility associated dyspepsia also mayexperience bloating, nausea, burping and a feeling of fullness thatoccurs soon after eating. It is an extremely common symptom complex,affecting as much as one-fourth of the United States adult population.

There are other disorders affecting the gastrointestinal tract that arecharacterized by abnormal tissue conditions not associated with neuralabnormalities.

SUMMARY OF THE INVENTION

One aspect of the invention provides a method of treating tissue withina body. The method comprises selecting at least one treatment agentcomprising at least one of a vanilloid compound and a cytokine compound.The method provides a source of the treatment agent. The method includesdeploying an endoscope to a targeted tissue region. The endoscope has aninterior lumen. The method includes visualizing the targeted tissueregion with the endoscope and deploying through the interior lumen ofthe endoscope a catheter carrying on its distal end a tissue-piercingelement adjacent to the targeted tissue region visualized by theendoscope. The method includes coupling the catheter to the source ofthe treatment agent, and applying through the tissue-piercing elementthe treatment agent into contact with the targeted tissue regionvisualized by the endoscope.

In one embodiment, the method injects the treatment agent intosubsurface tissue in the targeted tissue region.

In one embodiment, the method includes providing a guide wire tofacilitate deployment of the endoscope and/or catheter.

Features and advantages of the inventions are set forth in the followingDescription and Drawings, as well as in the appended Claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B are schematic views of a system for treating tissue thatincludes a treatment device with a tissue piercing member that embodiesfeatures of the invention, FIG. 1A showing the treatment device deployedin a tissue region and FIG. 1B showing the treatment device piercing thetissue region to inject a treatment agent;

FIGS. 2A and 2B are schematic views of a system for treating tissue thatincludes a treatment device with multiple tissue piercing members thatembodies features of the invention, FIG. 2A showing the treatment devicedeployed in a tissue region and FIG. 2B showing the treatment devicepiercing the tissue region to inject a treatment agent;

FIG. 3 is an embodiment of a tissue treatment device that takes the formof a syringe and a needle for injecting a treatment agent into a tissueregion that can be visualized from outside the body; and

FIG. 4 is an embodiment of a tissue treatment device for injecting atreatment agent into a tissue region that cannot be visualized fromoutside the body.

The invention may be embodied in several forms without departing fromits spirit or essential characteristics. The scope of the invention isdefined in the appended claims, rather than in the specific descriptionpreceding them. All embodiments that fall within the meaning and rangeof equivalency of the claims are therefore intended to be embraced bythe claims.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

This Specification discloses various systems and methods for treatingdysfunctions of organs or tissue in the gastrointestinal tract. Still,it should be appreciated that the disclosed systems and methods areapplicable for use in treating other dysfunctions elsewhere in the body,e.g., for treating sphincter barrier dysfunctions in the lowergastrointestinal tract or in the upper gastrointestinal tract. Thesystems and methods that embody features of the invention are adaptablefor use with catheter-based systems and surgical techniques, as well assystems and surgical Techniques that are not necessarily catheter-based.

I. System Overview

A tissue treatment system 10 that embodies features of the invention isshown in FIGS. 1A and 1B. The tissue treatment system 10 includes atissue treatment device 12 and an apparatus 14 to deliver the tissuetreatment device 12 to a tissue region 16 targeted for treatment. Thetreatment system 10 also includes a source 18 of a treatment agent 20.

A. The Tissue Treatment Device

The tissue treatment device 12 serves to apply the treatment agent 20 tothe targeted tissue region 16 to obtain a desired therapeutic effect.The therapeutic effect can comprise either alteration of nerve impulsepathways in the region 16 or a physical alteration of tissuecharacteristics in the region 16.

The tissue treatment device 12 includes one or more agent delivery ports22. The one or more delivery ports 22 can apply the treatment agent 20to surface tissue in the region 16. Desirably (as FIG. 1A shows), theport 20 is located at the end of a tissue piercing member 24. In thisarrangement, the treatment agent 20 may be injected into subsurfacetissue.

The tissue treatment device 12 can include single or multiple ports 22located single or multiple tissue piercing members 24 to inject thetreatment agent 20. As FIGS. 1A and 1B show, a single tissue piercingmember 24 (with a single port 22) may be used. Alternatively, as FIGS.2A and 2B show, the treatment device 24 can carry multiple tissuepiercing members 24, each with a port 22. Desirably, the multiple tissuepiercing members 24 are arranged in a spaced-apart array, to apply thetreatment agent 20 in a prescribed pattern at the targeted site.

Alternatively, the tissue treatment device 12 may employ air powered,needle-less injection technology.

B. The Delivery Device

The configuration of the delivery apparatus 14 for the device 12 canalso vary, depending upon the accessibility of the treatment site andthe particular treatment objectives desired.

If the treatment site can be directly visualized the delivery apparatus14, the source 18, and the treatment device 12 can comprise a syringe100 and a needle 102, as FIG. 3 shows.

If the treatment site can not be directly visualized or is otherwise notas readily accessible, the delivery apparatus 14 can comprise anendoscope 106 having an interior lumen 104 passed down the esophagusthrough the mouth, as FIG. 4 shows. In this arrangement, the treatmentdevice 12 is desirably carried on the distal end of a catheter tube 108for passage through the endoscope lumen 104 to the targeted site. Aguidewire may be used, if desired, to further facilitate deployment ofthe endoscope and treatment device to the targeted site.

C. The Tissue Treatment Agent

The treatment agent 20 is selected from a group of candidate agentsbased upon the physiologic effect or effects that are desired. One ormore candidate agents may be applied, either as a primary treatmentmodality, a neoadjuvent treatment modality, or an adjuvent treatmentmodality.

In the illustrated embodiment, the group consists essentially of twocandidate agents: (1) Vanilloid Compounds, and (2) Cytokine Sub-Types.

1. Vanilloid Compounds

The treatment agent 20 can comprise a vanilloid compound. Vanilloidcompounds have a unique capacity to bind to a membrane receptor insensory neurons. Capsaicin is one of many vanilloid compounds. Capsaicinis a powerful basic compound which is derived from chili peppers.

The specific neuron for capsaicin is deemed “VR1”. This receptor isexpressed only on small unmyelinated C-fibers (nerves typically involvedin special visceral sensation and pain).

Exposure to vanilloid compounds variably reduces the responsiveness ofthe neuron to stimuli. In many cases, the neuron may actually degenerateeither temporarily or permanently, thus impairing transmission of painsignals or other special sensory signals.

The term “vanilloid compound” as used herein means a compound or amixture of compounds having a biologically active vanillyl group.vanilloid compounds include both naturally occurring vanilloids,synthetic vanilloids, pharmaceutically acceptable salts of the vanilloidcompound (whether natural or synthetic) as well as pharmaceuticallyacceptable derivatives and/or analogues thereof (whether natural orsynthetic). Examples of natural vanilloid compounds include both thecrude extracts and the purified extracts of active vanilloid compoundsfrom: capsicum, cayenne pepper, black pepper, paprika, cinnamon, clove,mace, mustard, ginger, turmeric, papaya seed and the cactus-like plantEuphorbia resinifera.

Synthetic vanilloid compounds such as synthetic capsaicin are disclosedin WO 96/40079, which is incorporated herein by reference. The vanilloidcompound family includes: Capsaicin; Dihydrocapsaicin:Nordihydrocapsaicin; Homocapsaicin: Homodihydrocapsaicin. Alternatively,resiniferotoxin (RTX) is derived from the euphorbia cactus and isconsidered a capsaicin-like compound. This substance also activates theVR1 receptor and attenuates or eliminates afferent nerve function,although it may not illicit the rapid heat sensation that othervanilloids produce.

Other examples of vanilloid compounds include capsaicin((E)-(N)-[(4-hydroxy-3-methoxyphenyl)-methyl]-8-methyl-6-nonenamide);eugenol (2-methoxy-4-(2-propenyl)phenol); zingerone(4-(4-hydroxy-3-methoxyphenyl)-2-butanone); curcumin(1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione); piperine(1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine);resiniferatoxin(6,7-deepoxy-6,7-didehydro-5-deoxy-21-dephenyl-2l-(phenylmethyl)-20-(4-hydroxy-3-thoxybenzeneacetate))or pharmaceutically effective salts, analogues, derivatives orequivalents thereof.

The treatment agent 20 can include capsaicin, another vanilloidcompound, RTX, or combination thereof, alone or in combination withother substances (which will be generically called avanilloid-containing treatment agent 20).

The vanilloid-containing treatment agent can be applied through the port22 or ports 22 to the mucosal lining or extrinsically to the outside ofan organ. The vanilloid-containing treatment agent can also be injectedinto the targeted tissue region or organ wall.

The treatment agent 20 can be a solution, a gel, a powder, a pellet, orother form. The treatment agent may be released immediately, or, be asustained release product such as a slow released implant, slow releasegel, coated pellet, microsphere, or other form.

The vanilloid-containing treatment agent 20 may be applied or injectedas primary therapy, or, as a neoadjuvant or adjuvant procedure. Forexample, RF energy may be used to incite a wound, followed byapplication of the vanilloid-containing treatment agent to facilitateexuberant wound healing.

In dyspepsia and irritable bowel syndrome, the use of avanilloid-containing treatment agent can serve to diminish the painimpulses or could attenuate the dysmotility and alleviate the diseasestate.

An example of vanilloid materials that can be used is produced byAfferon and is called RTX, which has been instilled into the lumen ofthe urinary bladder for the treatment of urge incontinence. There arealso several topical, over-the-counter capsaicin products for topicalanalgesic applications.

2. Cytokine Sub-Types

The treatment agent 20 can include one or more subtypes of cytokines. Acytokine, in the natural state within the body, is a protein producedand released by a biological cell that has an effect on the localenvironment surrounding the cell. Cytokines are involved in manycellular processes, such as wound healing. The mechanism of action woulddepend on the specific cytokine utilized.

The term “cytokine subtype” as used herein means any polypeptide thataffects the functions of other cells, and is a molecule which modulatesinteractions between cells in the immune or inflammatory response. Acytokine subtype includes, but is not limited to monokines andlymphokines regardless of which cells produce them. For instance, amonokine is generally referred to as being produced and secreted by amononuclear cell, such as a macrophage and/or monocyte but many othercells produce monokines, such as natural killer cells, fibroblasts,basophils, neutrophils, endothelial cells, brain astrocytes, bone marrowstromal cells, epideral keratinocytes, and B-lymphocytes. Lymphokinesare generally referred to as being produced by lymphocyte cells.Examples of cytokine subtypes include, but are not limited to,interleukin-1. (IL-1), tumor necrosis factor-alpha (TNF alpha) and tumornecrosis factor beta (TNF beta).

Other cytokine subtypes include TGF-β(transforming growth factor β);PDGF (platelet derived growth factor) b-FGF (basic fibroblast growthfactor): IGF-1 (insulin-like growth factor 1); EGF (epidermal growthfactor); and VEGF. Some of these cytokines are available commercially,could be produced commercially, or can be extracted from a personsharvested platelets (platelet releasates). The effects of a givencytokine upon tissue physiology can include one or more of thefollowing: smooth muscle and fibroblast mitogenic effects (inducesdivision and growth of cells); stimulation of the release of cytokinesfrom other cells; chemoattractant (bringing new healing cells into localregion); decrease of collagen enzyme activity allowing collagen to buildup; inflammation; and angiogenesis (development of new blood vessels).

The treatment agent 20 can include a cytokine sub-type or combination ofcytokine sub-types, alone or in combination with other substances. Thecytokine-containing treatment agent can be applied by the port or ports22 to the tissue or organ wall, or injected into the tissue or organwall.

The cytokine-containing treatment agent 20 can be a solution, a gel, apowder, a pellet, or other form. The treatment agent may be releasedimmediately, or, be a sustained release product such as a slow releasedimplant, slow release gel, coated pellet, microsphere, or other form.

The cytokine-containing agent 20 may be applied or injected as primarytherapy, or, as a neoadjuvant or adjuvant procedure. For example, radiofrequency (RF) energy may be used to induce the wound healing process,followed by cytokine application to facilitate more exuberant woundhealing.

The application of a single cytokine or mixture thereof, as primary,neoadjuvant, or adjuvant therapy for abnormal tissue conditions (e.g.,excess tissue volume) could have the various mechanical and therapeuticeffects. With or without an inciting wound event (such as RF), cytokinescan serve to initiate the process of healing within the local region.This process includes, but is not limited to, influx of white bloodcells and macrophages, stimulation of fibroblast and smooth muscledivision and collagen secretion, new blood vessel growth, woundcontraction and tightening, maturation of the new or existing collagenframework, and reduced tissue compliance. These tissue effects couldimprove the compliance and reduce the tissue volume.

Examples of cytokine materials that can be used include commerciallyavailable Regranex, which is recombinant human PDGF-BB. This materialhas been applied as a gel for promoting the healing of diabetic footulcers. Platelet granules contain many of the cytokines listed above,and the cytokines can be extracted with a fairly simple technique(platelet releasates). Platelets (harvested as a pooled platelet productor from autologous donation) provide a source of cytokines forextraction. TGF-β and PDGF are considered to be the most importantsubstances for the purpose of initiating the wound healing process.

Various features of the invention are set forth in the following claims.

1. A method of treating tissue within a body comprising selecting atleast one treatment agent comprising at least one of a vanilloidcompound and a cytokine compound, providing a source of the treatmentagent, deploying an endoscope to a targeted tissue region the endoscopehaving an interior lumen, visualizing the targeted tissue region withthe endoscope, deploying through the interior lumen of the endoscope acatheter carrying on its distal end a tissue-piercing element adjacentto the targeted tissue region visualized by the endoscope, coupling thecatheter to the source of the treatment agent, and applying through thetissue-piercing element the treatment agent into contact with thetargeted tissue region visualized by the endoscope.
 2. A methodaccording to claim 1 wherein the applying includes injecting thetreatment agent into subsurface tissue in the targeted tissue region. 3.A method according to claim 1 further including providing a guide wireto facilitate deployment of the endoscope and/or catheter.